Compositions of Lipid Nanoparticles for Plasmid DNA Delivery to the Liver and Methods for Preparing the Same

Value Proposition:

·        Library screen of lipid nanoparticles to develop compositions for efficient transfection and tissue-specific delivery.

·        Selected high efficiency lipid nanoparticles for delivering plasmid DNA, siRNA, and mRNA. 

Technology Description

·        Researchers at Johns Hopkins have developed a multi-step screening method to optimize the composition of lipid nanoparticles (LNPs) for nucleic acid delivery. The researchers developed a screen of 1,080 LNP formulations for selection of efficient transfection. Each LNP is analyzed via a high-throughput in vitro and in vivo screen to identify top candidates based on cytotoxicity and transfection efficiency. Further testing is performed on top-performing LNP hits to select for the desired effects. Their findings highlight the importance of screening for lipid nanoparticles to tailor potent nucleic acid delivery in gene therapy treatments. 

Unmet Need

·        Lipid nanoparticles hold high potential as non-viral vectors for nucleic acid and drug delivery. There has been substantial progress in mRNA-based therapeutics, as evidenced by recently approved mRNA LNP vaccines approved for use for SARS-CoV-2. LNP compositions are critical for in vivo transfection efficiency, tissue-specific delivery and immune activation profile. However, there have been limited reports on analyzing LNPs in a high-throughput manner. Therefore, there is a strong need for the development of a lipid nanoparticle screening platform that can select formulations with optimal nucleic acid delivery for gene therapy and immunotherapy.

Stage of Development

·        The screen has been developed and selected compositions have shown efficacy for delivery, transfection of nucleic acids and inducing potent antitumor effect.

Data Availability

·        Data available upon request.

Publication

·        Zhu, Y., Shen, R., Vuong, I. et al. Multi-step screening of DNA/lipid nanoparticles and co-delivery with siRNA to enhance and prolong gene expression. Nat Commun 13, 4282 (2022).

·       Zhu, Y., Ma, J., Shen, R. et al. Screening for lipid nanoparticles that modulate the immune activity of helper T cells towards enhanced antitumour activity. Nat. Biomed. Eng (2023).